Tackling Nontuberculous Mycobacteria by Repurposable Drugs and Potential Leads from Natural Products.

Nontuberculous Mycobacteria (NTM) refer to bacteria other than all Mycobacterium species that do not cause tuberculosis or leprosy, excluding the species of the Mycobacterium tuberculosis complex, M. leprae and M. lepromatosis. NTM are ubiquitous and present in soils and natural waters. NTM can survive in a wide range of environmental conditions. The direct inoculum of the NTM from water or other materials is most likely a source of infections. NTMs are responsible for several illnesses, including pulmonary alveolar proteinosis, cystic fibrosis, bronchiectasis, chronic obstructive pneumoconiosis, and pulmonary disease. Recent reports suggest that NTM species have become insensitive to sterilizing agents, antiseptics, and disinfectants. The efficacy of existing anti-NTM regimens is diminishing and has been compromised due to drug resistance. New and recurring cases of multidrug-resistant NTM strains are increasing. Thus, there is an urgent need for ant-NTM regimens with novel modes of action. This review sheds light on the mode of antimicrobial resistance in the NTM species. Then, we discussed the repurposable drugs (antibiotics) that have shown new indications (activity against NTM strains) that could be developed for treating NTM infections. Also, we have summarised recently identified natural leads acting against NTM, which have the potential for treating NTM-associated infections.

Nanoencapsulation of triterpene 3ß,6ß,16ß-trihydroxylup-20(29)-ene from Combretum leprosum as strategy to improve its cytotoxicity against cancer cell lines.

The pentacyclic triterpene 3ß,6ß,16ß-tri-hydroxilup-20(29)-ene is a natural product produced by the Brazilian medicinal plant Combretum leprosum. Its cytotoxicity has been previously reported against breast cancer cell lines. The low water solubility of this natural product, that hampers its bioavailability, motivated the investigation of a new nanoparticle formulation containing the triterpene in order to improve its bioactivity. The triterpene was encapsulated in polycaprolactone (PCL) polymer by nanoprecipitation, producing homogenic nanoparticles with nanometer sizes (122.7 ± 2.06 nm), which were characterized by FT-IR, SEM imaging and DSC. The cytotoxicity (MTT method) of the nanoparticle containing the triterpene 1, besides the free natural product and the nanoparticle control (without 1), was assayed against three human tumor cell lines [human colon carcinoma line (HCT116), prostate (PC3) and glioblastoma (SNB19)] and the normal epithelial embryo kidney human cell line (Hek293T). The nanocarrier produced a significative effect in the cytotoxicity of the natural product in the nanoformulation (IC50 0.11-0.26 µg mL-1) when compared with its free form (IC50 1.07-1.44 µg mL-1). Additionally, higher selectivity of the triterpene to the tumor cells was found when it was encapsulated (SI 1.92-4.54) than in its free form (SI 0.42-0.56). In this case, the nanoencapsulated triterpene was more selective to PC3 (SI 3.33) and SNB19 (SI 4.54) tumor cells.